Induction of Programmed Cell Death in Acanthamoeba culbertsoni by the Repurposed Compound Nitroxoline
Abstract
:1. Introduction
2. Materials and Methods
2.1. Molecules
2.2. Acanthamoeba spp. Strains
2.3. In Vitro Effect against the Trophozoite Stage
2.4. In Vitro Effect against the Cyst Stage
2.5. Evaluation of Actin Distribution
2.6. Immunofluorescence Staining of Intracellular Tubulin in Acanthamoeba culbertsoni
2.7. In Vitro Labelling of Autophagic Vacuoles in Acanthamoeba culbertsoni
2.8. Proteomic Analysis of the Effect of Nitroxoline in Acanthamoeba Castellanii L-10 Trophozoites
2.8.1. Comparative Label-Free Proteomics
2.8.2. Protein Digestion
2.8.3. nLC-MS 2 Analysis
2.8.4. Data Analysis
2.9. Evaluation of Nitroxoline Mechanism of Action
2.9.1. Analysis of Mitochondrial Function Disruption
2.9.2. Measurement of ATP Production
2.9.3. Chromatin Condensation Detection
2.9.4. Plasma Membrane Permeability
2.9.5. Evaluation of Intracellular ROS Production
2.10. Statistical Analysis
3. Results
3.1. In Vitro Activity of Nitroxoline against Trophozoites and Cysts of Acanthamoeba spp.
Evaluation of Nitroxoline Effect on Cellular Events
3.2. Nitroxoline Affects Both Cellular Morphology and Cytoskeleton Structure in Fixed Cells
3.3. Visualization of Autophagic Vacuoles in A. culbertsoni Using the Dye Monodansylcadaverine
3.4. Nitroxoline Effect on the Proteomic Profile of Acanthamoeba Castellanii L-10
3.5. Nitroxoline Causse Mitochondrial Dysfunction in A. culbertsoni
3.5.1. Nitroxoline Prevents the Aggregation of the JC-1 Dye
3.5.2. Nitroxoline Induces a Decrease in the ATP Levels
3.6. In Vitro Determination of the Cell Death Mode Induced by the Nitroxoline
Analyzing Cell Death by Double Nuclear Staining with Hoechst 33342/PI
3.7. Nitroxoline Could Alter Plasma Membrane Permeability in Treated Cells
3.8. Nitroxoline Increases the Cytosolic Level of Reactive Oxygen Species (ROS) in A. culbertsoni
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Acanthamoeba Strains | Nitroxoline IC50 (µM) | Chlorhexidine IC50 (µM) | Voriconazole IC50 (µM) | |||
---|---|---|---|---|---|---|
Trophozoites | Cysts | Trophozoites | Cysts | Trophozoites | Cysts | |
A. castellanii Neff | 0.87 ± 0.19 aA | 0.28 ± 0.12 aA | 3.02 ± 0.89 aB | 5.97 ± 1.76 cC | 0.99 ± 0.04 aA | 3.45 ± 0.17 bB |
A. polyphaga | 0.95 ± 0.01 aA | 0.81 ± 0.03 aA | 5.59 ± 0.04 bB | 9.41 ± 0.16 dC | 1.07 ± 0.02 aA | 6.98 ± 0.05 cB |
A. griffini | 0.69 ± 0.01 aA | 0.84 ± 0.01 aA | 5.60 ± 0.07 bB | 7.38 ± 1.94 cB | 0.32 ± 0.01 aA | 0.92 ± 0.06 aA |
A. quina | 3.24 ± 0.56 bB | 0.31 ± 0.05 aA | 5.31 ± 0.48 bCB | 4.04 ± 0.48 b | 0.54 ± 0.01 aA | 4.69 ± 0.09 bB |
A. L-10 | 2.85 ± 0.58 bB | 0.11 ± 0.03 aA | 9.11 ± 0.29 dC | 1.30 ± 0.36 aA | 1.77 ± 0.15 abA | 0.51 ± 0.10 aA |
A. culbertsoni | 1.17 ± 0.09 aA | 0.98 ± 0.23 aA | 8.11 ± 0.17 cC | 2.92 ± 0.28 bB | 1.93 ± 0.09 bB | 1.24 ± 0.15 aA |
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Rodríguez-Expósito, R.L.; Sifaoui, I.; Reyes-Batlle, M.; Fuchs, F.; Scheid, P.L.; Piñero, J.E.; Sutak, R.; Lorenzo-Morales, J. Induction of Programmed Cell Death in Acanthamoeba culbertsoni by the Repurposed Compound Nitroxoline. Antioxidants 2023, 12, 2081. https://doi.org/10.3390/antiox12122081
Rodríguez-Expósito RL, Sifaoui I, Reyes-Batlle M, Fuchs F, Scheid PL, Piñero JE, Sutak R, Lorenzo-Morales J. Induction of Programmed Cell Death in Acanthamoeba culbertsoni by the Repurposed Compound Nitroxoline. Antioxidants. 2023; 12(12):2081. https://doi.org/10.3390/antiox12122081
Chicago/Turabian StyleRodríguez-Expósito, Rubén L., Ines Sifaoui, María Reyes-Batlle, Frieder Fuchs, Patrick L. Scheid, José E. Piñero, Robert Sutak, and Jacob Lorenzo-Morales. 2023. "Induction of Programmed Cell Death in Acanthamoeba culbertsoni by the Repurposed Compound Nitroxoline" Antioxidants 12, no. 12: 2081. https://doi.org/10.3390/antiox12122081